Updated information on MRSA infections

Many people mistake the first signs of methicillin-resistant Staphylococcus aureus (MRSA) infection for a spider bite. In fact, what appears as a small, red pimple could be the start of a potentially serious infection with a staphylococcus that is impervious to many antibiotics and poses an increasing threat in the community setting.


Scientists first discovered S. aureus in the 1880s.¹ Traditionally, the bacterium has caused skin and tissue infections, but it can also cause food poisoning and, in more serious cases, bacterial pneumonia or septicemia.


In the late 1940s, S. aureus began a dangerous evolution when it became resistant to penicillin. With their primary weapon against the organism taken out of commission, clinicians began using methicillin, a relative of penicillin, to treat S. aureus infections. But in 1961, scientists got some bad news with the discovery of S. aureus strains that had become resistant to beta-lactams, including amoxicillin and methicillin, giving MRSA its name.¹


MRSA History


The first infection involving MRSA in the United States was diagnosed in 1968, and the organism has continued to evolve ever since. Beginning in 2002, there have been a handful of cases documented in which the bacterium was also found to be resistant to one of the last available drugs being used to treat it — vancomycin (Vancocin).


Despite that ominous development, there has recently been encouraging news from the CDC that hospital-acquired MRSA (HA-MRSA) infections are decreasing.² The number of invasive HA-MRSA infections dropped 28% between 2005 and 2008. Unfortunately, the same is not true of community-acquired MRSA (CA-MRSA) cases, which have risen rapidly in the past 10 years.² Because MRSA is circulating widely in the general population, primary-care clinicians must be prepared to recognize it, treat it effectively and take steps to reduce its transmission.

Community-acquired MRSA


Historically, most cases of MRSA infection occurred in the hospital setting, but in 1982, cases began cropping up in community settings among individuals who had not been hospitalized. The first domestic cluster involved a group of IV-drug users in Detroit. A second cluster of drug users was infected in 1992, and the prevalence of CA-MRSA began to increase in the community at large in the mid-1990s.


Most CA-MRSA cases have originated in prisons, day-care centers and athletic or military facilities. But MRSA is not limited to those sites. It has also been found in other locations, including Washington State beaches and marine water.


CA-MRSA typically causes skin and soft-tissue infections (Figure 1), often in young and otherwise healthy patients. These infections are typically easier to treat than HA-MRSA infections, but some patients with CA-MRSA develop such serious conditions as necrotizing pneumonia, disseminated invasive osteomyelitis, septic arthritis or endocarditis.³


While the majority of CA-MRSA cases are more easily treated than HA-MRSA cases, the bacterium responsible for CA-MRSA is actually more virulent than its hospital counterpart. Three different S. aureus strains typically cause community infection, which often involves a variety of toxins including leukocyte toxins, exfoliative toxins and exotoxins, making the causative organisms highly virulent pathogens.



Risk factors for CA-MRSA infections


MRSA colonization is a risk factor for infection, although the link between colonization and infection needs further investigation. The organism is sometimes found on the skin or carried inside the nose of healthy individuals.

An estimated 25% to 30% of people carry colonies of staphylococci in their noses, according to the CDC, but less than 2% are colonized with MRSA.² Most health-care professionals who are colonized with MRSA spontaneously clear the organism from their systems without ever developing an infection.


Other risk factors for infection include:

• Close skin-to-skin contact with other individuals 

• Cuts or abrasions on the skin 

• Contact with contaminated items or surfaces 

• Living in crowded conditions 

• Poor hygiene.⁴ 


People who come into contact with farm animals may also be at greater risk for infection. Pigs, cattle, and poultry are increasingly being found with a new clone of MRSA, CC398. And farm animals are not the only ones becoming infected. Rates of MRSA are also up among household pets, such as dogs and cats.


While people can contract MRSA infections from many different sources, the most common route to infection remains transmission through direct skin-to-skin contact. Clinicians should remember that when it comes to MRSA, essentially everyone is at risk.


Clinical presentation and treatment

Most patients with CA-MRSA will present with a skin or soft-tissue infection. Clinicians should assume that any spider bite, large pimple, or boil is MRSA until they have evidence to the contrary.



The first step in treating MRSA infections is to incise and drain the area. This may be sufficient to treat abscesses <5 cm in diameter. The clinician should send a sample of the material collected for culture and sensitivity. Once the incision and drainage is complete, antibiotic treatment should be considered.


IV antibiotics

A number of IV antibiotics can effectively treat MRSA infections, including the following:


• First-line therapy: vancomycin. Appropriate dosage is 30 mg/kg, but the dose should not exceed 2 g in any 24-hour period. It is important to administer vancomycin slowly over 90 minutes to prevent “red man syndrome,” a hypersensitivity reaction linked to rapid administration of the antibiotic.⁵

• Second-line therapy: daptomycin (Cubicin). Proper dosage is 4 to 6 mg/kg administered via IV piggyback every 24 hours. This drug has been shown to be safe, although it can occasionally cause elevations in creatine kinase levels.

• Third-line therapy: linezolid (Zyvox). Dosage is 600 mg every 12 hours. Linezolid is a monoamine oxidase inhibitor that offers 100% bioavailability. Zyvox is very expensive, although the oral formulation has shown a cost savings for outpatient treatment.⁶ The usefulness of linezolid is limited by its cost and toxicity as well as the potential for the organism to develop resistance to the drug. Possible side effects related to treatment include thrombocytopenia, peripheral and optic neuropathy, and lactic acidosis in patients receiving prolonged therapy.

• Fourth-line therapy: tigecycline (Tygacil). Dosage is 100 mg IV once, then 50 mg IV every 12 hours. This drug has a broader spectrum of antimicrobial activity.

• Fifth-line therapy: quinupristin/dalfopristin (Synercid).


In addition to the antibiotics listed above, a number of emerging therapies may be useful for the treatment of MRSA, including dalbavancin, telavancin (Vibativ, Theravance), and ceftobiprole.


Oral antibiotics

Some antibiotics available in oral formulations are treatment options for MRSA:


• First-line therapy: trimethoprim-sulfamethoxazole (TMP-SMX; Bactrim DS, Septra DS. Sulfamethoprim-DS). This agent has been shown to be 95% effective.

• Second-line therapy: clindamycin (Cleocin). Keep in mind that the organism may develop resistance to this drug, particularly if it is resistant to erythromycin. Also remember that patients exposed to clindamycin are at risk for infection with Clostridium difficile.

• Third-line therapy: tetracycline or doxycycline/minocycline (Dynacin, Minocin). This agent is administered for 21 days.

• Fourth-line therapy: linezolid.

• Rifampin (Rifadin) may also be used. It is typically effective in combination with other drugs. Because rifampin achieves high concentrations in mucosal surfaces, its inclusion in a regimen to treat MRSA is theoretically beneficial.


Drugs to be avoided

Erythromycin (Ery-tab, PCE) and cephalexin (Keflex) are ineffective against MRSA, and ciprofloxacin (Cipro) and levofloxacin (Levaquin) are to be avoided because rates of MRSA infection are increased in hospitalized patients treated with quinolones. Bacitracin and neomycin, two common ingredients in OTC antibacterial ointments, are not recommended for the treatment of MRSA, although a recent study indicates that they may be effective against a specific clone of MRSA.⁷


Empiric MRSA coverage is not necessary for children who have uncomplicated skin infections. Researchers found no difference in outcome between children randomly assigned to receive cephalexin, an antibiotic without MRSA activity, or clindamycin. The children received cephalexin 40 mg/kg/day in three divided doses or clindamycin 20 mg/kg/day also in three divided doses for seven days.⁸



Decolonization


While the CDC does not routinely recommend decolonization,⁹ this treatment may be advisable in certain circumstances. For example: (1) patients who are immunocompromised (e.g., those with leukemia, another cancer or HIV) and might develop particularly life-threatening infections; and (2) patients who live in close quarters with others, such as in mental institutions, prisons or military barracks.


Decolonization can be accomplished by washing with chlorhexidine (Hibiclens, Exidine, CIDA-STAT). Hexachlorophene (Phisohex) can also be used, but only in combination with mupirocin (Bactroban), not by itself. Mupirocin ointment placed in the nostrils twice daily for seven days will also result in decolonization. 


Mupirocin nasal ointment plus bleach baths (one tablespoon of bleach in one quart of water) will achieve long-term S. aureus decolonization of the skin. Some strains of MRSA are resistant to mupirocin (mupA gene found on USA300 MRSA clones).


New nondrug therapies are also being considered for their potential to combat MRSA. These include lemongrass essential oil, which research has shown to be effective in completely inhibiting all MRSA colony growth.¹⁰ Tea tree oil also has been shown to be effective. There is clinical evidence that topical preparations may be more effective than conventional antibiotics in preventing transmission of CA-MRSA.¹¹


Another substance being considered to combat MRSA is French clay. The clay has been found to kill several types of bacteria, and researchers recently discovered that specific minerals in the clay are toxic to MRSA.¹²

Treating complications


Not all patients with MRSA cellulitis will respond to initial treatment, and clinicians must recognize when patients need more aggressive treatment or hospitalization. Patients who meet at least two of the following criteria may need hospital treatment:


• Fever >100.4°F 

• WBC count >13,000/µL 

• Bands >10% 

• Hand cellulitis 

• Facial cellulitis 

• Immunocompromise 

• Older than age 70 years 

• Failing outpatient treatment 


Another warning sign is the presence of cellulitis with no drainable pus. This raises concern of group A streptococcal infection. In this instance, clinicians should keep in mind that TMP-SMX and doxycycline, both of which are effective against MRSA, are less effective against group A streptococcus.

Therefore, treatment should also include amoxicillin, ampicillin or penicillin. Use of clindamycin should also be considered in these cases because it may be effective against both MRSA and group A streptococcus. The typical regimen for treating a co-infection should include vancomycin and clindamycin.



Preventing transmission


When treating patients with MRSA infections, health-care workers should take care to reduce the risk of spreading the organism to others. Standard precautions will help accomplish this goal.


Clinicians must be certain to wash their hands before and after examining patients, and they should wear gloves anytime they might come into contact with blood, body fluids, secretions or contaminated items. The gloves should be removed immediately after use to prevent transfer of microorganisms. Health-care workers who do not remove gloves quickly could contaminate environmental surfaces or spread the organism to other patients.

For example, if a clinician examines a patient and then touches a drawer, chart, or doorknob without removing his or her gloves, those surfaces may become contaminated, and the organism may be spread. MRSA can live on some surfaces for hours or even days. 


Clinicians should wash their hands after each examination whether they wore gloves or not. 


In addition to gloves, other personal protective equipment should be used to prevent the spread of MRSA. Practitioners should wear masks and eye protection to prevent body fluids and blood from spraying into mucous membranes of the provider’s eyes, nose and mouth during procedures or patient-care activities. Clinicians should also wear a disposable gown, both to protect their skin and to prevent their clothing from becoming contaminated during patient care.


Any patient-care equipment that has been soiled with blood, body fluids, secretions or excretions must be handled properly to avoid transferring microorganisms to other patients and environments. The same is true for linens. Additionally, rooms used by patients with MRSA must undergo terminal cleaning.


A new disinfecting tool may be on the horizon, however. Aerosolized hydrogen peroxide has been shown to neutralize MRSA on environmental surfaces.¹³ Studies have demonstrated that the hydrogen peroxide is nearly 100% effective and that its disinfecting effect lasts for weeks. Aerosolized hydrogen peroxide is also cost-effective, making it a promising new infection-control measure.



Alternate strategies


In addition to environmental cleaning, clinicians may want to explore other methods for reducing MRSA transmission, including:


• Aggressively screening health-care workers for MRSA colonization 

• Performing active-surveillance cultures for MRSA in at-risk patients and putting those who test positive on contact precautions. 


Ultimately, managing MRSA requires a comprehensive approach that includes prevention, timely treatment and efforts to reduce transmission. The more informed clinicians are about how to undertake each of these steps, the more likely that the number of CA-MRSA cases will decline in the future. 


Joe Gilboy, PA-C, is a staff member in the emergency department at Hoag Hospital in Newport Beach, Calif. Gilboy has also served as an educational consultant to the physician assistant programs at Stanford University in Palo Alto, San Joaquin Valley College in Visalia and Loma Linda University in Loma Linda, all in California; and Touro University in Henderson, Nev. 



All electronic documents accessed December 5, 2011
.

From the December 01, 2011 Issue of Clinical Advisor